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Melanocytic Nevi (melanocytic + nevi)
Kinds of Melanocytic Nevi Selected AbstractsMEASURING CONGENITAL MELANOCYTIC NEVIPEDIATRIC DERMATOLOGY, Issue 2 2004Ramón Ruiz-Maldonado M.D. No abstract is available for this article. [source] BRAF V599E Mutation is Not Age Dependent: It is Present in Common Melanocytic Nevi in Both Children and AdultsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2005J. Cohen BRAF encodes a serine-threonine kinase, which acts in the RAS/RAF/MAPK pathway transducing regulatory signals from RAS to MEK1/2. Somatic mutations in BRAF have been identified in 53,80% of primary melanomas and 70,90% of common melanocytic nevi. More than 90% of these mutations consist of a valine to glutamate substitution at codon 599 (V599E) of exon 15. While a high prevalence of BRAF mutations in common melanocytic nevi has been reported in adults, nevi in children have not been studied. Of interest, we have previously shown that Spitz nevi in children do not harbor mutations in BRAF. To investigate the association of BRAF mutations with patient age, we studied common melanocytic nevi in children for the V599E activating mutation. Tumor cells were microdissected from 6 common melanocytic nevi in children 10 years of age or younger, and analyzed for the V599E mutation in BRAF by allele-specific PCR and gel electrophoresis. In 6 of 6 (100%) nevi, the V599E mutant allele was observed. Our data suggest that similar genetic pathways are involved in the development of common melanocytic nevi in children and adults. The absence of BRAF mutations in Spitz nevi in children is therefore associated with tumor type, not patient age. [source] Large Atypical Melanocytic Nevi in Recessive Dystrophic Epidermolysis Bullosa: Clinicopathological, Ultrastructural, and Dermoscopic StudyPEDIATRIC DERMATOLOGY, Issue 4 2005Fernando Gallardo M.D. The lesion was clinically atypical and fulfilled the criteria for a malignant melanocytic proliferation. A complete surgical excision was performed. Histopathologic examination disclosed a compound melanocytic nevus without melanocytic atypia. Ultrastructural examination showed melanocytic cells located both at the roof and the floor of the blister. Several months later, three pigmentary lesions with a similar clinical appearance developed. Periodic clinical and dermoscopic examinations were recommended. Dermoscopic examination disclosed a globular pattern with brown globules and black dots distributed all over the lesions. The lesions also exhibited blue-greyish dots and multiple rounded white structures corresponding to milia-like cysts. No dermoscopic features suggestive of malignancy were noted. Acquired melanocytic nevi showing atypical clinical features have been reported to occur in areas of blistering in patients with epidermolysis bullosa. These nevi appear as large, asymmetrical pigmentary lesions with irregular borders. Initially, they are very dark in pigmentation, with color variegation and loss of pigment, and even becoming papillomatous over time. Histopathologic examination can show features of compound/junctional nevus as well as persistent/recurrent nevus. The concept of "epidermolysis bullosa nevus" has been proposed to define these peculiar lesions. The clinical, histopathologic and ultrastructural features of these nevi are reviewed. The usefulness of dermoscopic examination in the routine diagnosis and follow-up of these lesions are stressed. [source] Melanocytic nevi are associated with neurofibromas in neurofibromatosis, type I, but not sporadic neurofibromas.JOURNAL OF CUTANEOUS PATHOLOGY, Issue 8 2005A study of 226 cases Background:, Neurofibromatosis, type 1, is associated with cutaneous melanin pigmentation, but an association with ordinary melanocytic nevi has not been described. Methods:, This retrospective case-control study was designed to see if neurofibromas in patients with neurofibromatosis, type 1 (NF-1) differ from sporadic neurofibromas (SN) in their incidence of associated melanocytic nevi and other histologic features. Slides from 114 NF-1 were compared with 112 SN and 300 intradermal melanocytic nevi (IDN). Results:, Small lentiginous melanocytic nevi were identified over 13 NF-1 (11%) but no SN (P = 0.0002). Compared with other NF-1, NF-1 with nevi were more frequently associated with melanocytic hyperplasia, giant melanosomes and diffuse neurofibroma (P < 0.03). Compared with SN, NF-1 were also more frequently associated with melanocytic hyperplasia, lentigo simplex-like changes, diffuse neurofibroma and plexiform neurofibroma (P < 0.001). Sebaceous hyperplasia (14%), dermal elastosis (9%), lipomatous change (8%), epithelial cysts (4%) and keratin granulomas or folliculitis (3%) were not significantly different in prevalence between NF-1, SN and the control group of IDN. Conclusions:, This study suggests that there is a difference in the potential for melanocytic proliferation in NF-1 compared with SN. NF-1, SN and IDN are associated with a similar range of incidental histologic changes. [source] Pleiotrophin expression correlates with melanocytic tumor progression and metastatic potentialJOURNAL OF CUTANEOUS PATHOLOGY, Issue 2 2005H. Wu Background:, Gene expression profiling of melanoma and nevic tissue has demonstrated that pleiotrophin (PTN) is significantly overexpressed in human melanomas. Methods:, To further evaluate PTN expression in melanocytic lesions, protein immunohistochemistry was performed on the spectrum of melanocytic lesions. Results:, Melanocytic nevi were consistently negative (n = 58). In contrast, the great majority of metastatic melanomas were positive (33/34, 97%). The analysis of 34 primary melanomas demonstrated PTN positivity in 20 lesions while 14 lesions were negative. Within the primary melanomas, PTN immunoreactivity was associated with metastasis (p = 0.0004) and decreased melanoma-related survival (p = 0.0444). Univariate analysis of PTN immunoreactivity predicted an increased risk for metastasis (relative risk 9.1, p = 0.003). Conclusions:, The results of this study confirm previous gene profiling data showing differential PTN expression between melanocytic nevi and melanomas. In addition, lesional PTN expression is associated with metastatic potential and may be a prognostic factor for melanomas. [source] Focal Regression-Like Changes in Dysplastic Back Nevi :A Diagnostic Pitfall for Malignant MelanomaJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2005A. Hassanein Regression in melanoma can be complete or partial. Melanocytic nevi may show focal regression-like changes (RLC). We studied the incidence of RLC in a total of 777 melanocytic back nevi. These included 17 cases of blue nevi, 28 cases of compound nevi, 385 cases of compound dysplastic nevi, 34 cases of congenital compound nevi, 26 cases of congenital intradermal nevi, 58 cases of intradermal nevi, and 229 cases of junctional dysplastic nevi. The dysplastic nevi were categorised according to the associated cytologic atypia (mild, moderate, and severe). 21 malignant melanomas of the back were also reviewed for regression. RLC were seen with a striking correlation with the degree of cytologic atypia in dysplastic nevi. RLC were seen in 4.5% of mildly, 9.6% of moderately, and 17.2% of severely dysplastic compound nevi. RLC were seen in 10.3% of mildly, 18.8% of moderately, and 39.3% of severely dysplastic junctional nevi. The incidence of regression in non-dysplastic nevi was much less, ranging from 2.9% to 3.6%. We believe this phenomenon is probably related to trauma/irritation. Caution should be taken before rendering the diagnosis of regressed malignant melanoma on the back since dysplastic nevi may show focal similar changes. [source] Melanocytic nevi of the breast: a histologic case-control studyJOURNAL OF CUTANEOUS PATHOLOGY, Issue 2 2004F. Rongioletti Background:, Melanocytic nevi in the genital, acral, and flexural sites often display clinical and histologic features that may simulate melanoma. We verified whether this is the case also for nevi of the breast. Methods:, Eleven dermatopathologists, from nine Italian Institutions, collected the specimens of melanocytic lesions from the breast and other body sites, excluding the acral, genital, and flexural areas, as controls. Cases and controls were matched for sex and age. All nevi were observed ,blindly' and simultaneously by all participants. For each lesion, 10 histological parameters were analyzed: asymmetry, absence of lateral demarcation of melanocytes, lentiginous proliferation, nested and dyshesive pattern, intraepidermal melanocytes above the basal layer, involvement of the hair follicle, absence of maturation of dermal melanocytes, melanocytic atypia, fibroplasia of the papillary dermis, and lymphocytic dermal infiltrate. Each parameter was scored 2 when present and 1 when absent or not valuable. A total score was calculated for each lesion. Results were statistically analyzed by the chi-square test and the Mann,Whitney U -test. Results:, One hundred and one nevi came from the breast area and 97 from elsewhere. Breast nevi exhibited significantly more atypical features than nevi from other sites. In particular, breast nevi with intraepidermal melanocytes, melanocytic atypia, and dermal fibroplasia were significantly more numerous. We did not find any sexual difference. Conclusions:, To avoid undue concerns, dermatopathologists should be aware that melanocytic nevi of the breast may show a high degree of atypical features. [source] MMP-2, TIMP-2 and MT1-MMP are differentially expressed in lesional skin of melanocytic nevi and their expression is modulated by UVB-lightJOURNAL OF CUTANEOUS PATHOLOGY, Issue 7 2002S. Krengel Background:, In malignant melanoma, recent studies have demonstrated an important role of matrix-metalloproteinase 2 (MMP-2), its co-activating enzyme membrane-type matrix-metalloproteinase 1 (MT1-MMP), and the endogenous inhibitor of MMP-2, tissue-inhibitor of matrix metalloproteinase 2 (TIMP-2). Melanocytic nevi are benign neoplasms of the melanocytic lineage, but may exhibit dysplastic features that can be difficult to distinguish from early stage melanoma. As shown in earlier studies, nevi show important morphological and phenotypical changes in response to ultraviolet light (UVB) irradiation. Objective:, To clarify the role of MMP-2, TIMP-2 and MT1-MMP in UVB-irradiated vs. non-irradiated melanocytic nevi. Methods:, Immunohistochemical comparison of the MMP-2, TIMP-2 and MT1-MMP expression pattern. Results:, MMP-2 is expressed by lesional keratinocytes and its expression is up-regulated by UVB-irradiation. MMP-2 expression was not observed in melanocytic cells. TIMP-2, by contrast, is predominantly expressed by melanocytic nevus cells, and its expression is in part down-regulated by UVB-irradiation. MT1-MMP is expressed by basal keratinocytes and to a weaker extent by melanocytic nevus cells. Conclusions:, MMP-2 expression by keratinocytes in nevi probably represents the result of activation of keratinocyte turnover in lesional epidermis. MMP-2 could play a role in the downward movement of junctional nevus cells into the dermis. The reduction of TIMP-2 expression in melanocytic cells by UV-light together with the enhanced expression of MMP-2 in the adjacent epidermis may promote basement membrane degradation. The expression pattern of MT1-MMP in close proximity to epithelial,mesenchymal interfaces underlines the synergistic role of MT1-MMP in this process. [source] Histopathological features of flexural melanocytic nevi: a study of 40 casesJOURNAL OF CUTANEOUS PATHOLOGY, Issue 5 2000Franco Rongioletti Melanocytic nevi in certain locations such as the genital and acral sites may have atypical histologic features simulating melanoma. We studied the microscopic findings of 40 melanocytic nevi of flexural sites (axilla, umbilicus, inguinal creases, pubis, scrotum and perianal area) to verify if flexural nevi show distinctive features similar to melanocytic nevi of the genital skin. The patients were young (mean age 20 years), the lesions were mostly removed for cosmetic reasons and we are not aware of any deaths or complications related to the removed nevi. We found that 22 (55.5%) out of 40 flexural nevi had "a nested and dyshesive pattern" similar to the melanocytic nevi of genital skin. This pattern was characterized by the confluence of enlarged nests with variation in size, shape and position at the dermo-epidermal junction and by the diminished cohesion of melanocytes. Dermatopathologists should pay attention to the "nested and dyshesive pattern" of flexural nevi that may mimick hystologic changes of melanoma. [source] Small and Medium-Sized Congenital Nevi in Children: A Comparison of the Costs of Excision and Long-Term Follow-UpDERMATOLOGIC SURGERY, Issue 12 2009FERNANDO ALFAGEME ROLDÁN MD BACKGROUND Clinical decisions on whether to follow up or remove small and medium congenital melanocytic nevi (SMCMN) in children have cost implications that have not been studied. OBJECTIVES To compare the costs of excision of SMCMN in children with lifelong follow-up in a tertiary center. METHODS AND MATERIALS We elaborated models for the evaluation of the costs of excision and long-term follow-up. We retrospectively collected data on 113 consecutive excised SMCMN (105 single-step interventions and 8 multiple-step interventions) from the medical records of our pediatric dermatology unit from 2001 to 2007 and calculated and compared the costs (direct and indirect) of surgery and follow-up. RESULTS The mean ± standard deviation and total cohort costs for single-step interventions were ,1,504.73 ± 198.33 and 157,996.20, respectively. Median and cohort lifelong follow-up costs were similar if performed every 4 years (1,482.66 ± 34.98 and 156,679.63). For multiple-step interventions (3 or 4 steps), surgery costs were similar to those of annual lifelong follow-up. In the case of two-step surgery, costs were similar to lifelong follow-up every 2 years. CONCLUSIONS An analysis of the costs of surgery and long-term follow-up in children with SMCMN is possible. Although the clinical judgment of the dermatologist and parental opinion are the main determinants in the management of SMCMN, costs should also be taken into account. [source] Regression of Atypical Nevus: An Anecdotal Dermoscopic ObservationDERMATOLOGIC SURGERY, Issue 10 2006MARIA A PIZZICHETTA MD BACKGROUND Clark nevi (atypical melanocytic nevi) can be considered as risk markers and potential precursors of melanoma. The authors report on the morphologic changes of an atypical nevus by dermoscopic follow-up examination over a 7-year period. CASE REPORT A 43-year-old man had a brown macule on his back, sized 5 mm, with an irregular shape, clinically and dermoscopically diagnosed as an equivocal melanocytic lesion. Dermoscopically during the initial examination, a predominant reticular pattern with peripheral eccentric hyperpigmentation in the lower portion of the lesion could be seen. After 7 months, the area of peripheral eccentric hyperpigmentation had regressed, and after 4.5 years the atypical pigment network had almost disappeared. After 7 years of follow-up, a diffuse area of hypopigmentation and a residual light brown pigmentation were detectable. The histopathologic diagnosis was consistent with an atypical junctional nevus with regression with features of a Clark nevus. CONCLUSION Based on our observation, even a dermoscopically atypical nevus may undergo regression as documented by long-term dermoscopic follow-up. [source] Treatment of melanocytic neviDERMATOLOGIC THERAPY, Issue 3 2005Harue Suzuki ABSTRACT:, Pigmented nevi are a heterogeneous group of lesions that range from uniquely curable with laser treatment, to partially responsive, to unresponsive or dangerous. This article presents laser and IPL treatment strategies from a clinical perspective for nevi organized by their typical responsiveness. A rationale for surgical excision, laser, and/or medical therapy in individual patients is also presented. Despite significant recent progress, it is clear that much understanding are still lacking about optimal laser treatment for pigmented lesions. [source] The increased expression of Y box-binding protein 1 in melanoma stimulates proliferation and tumor invasion, antagonizes apoptosis and enhances chemoresistanceINTERNATIONAL JOURNAL OF CANCER, Issue 10 2007Birgit Schittek Abstract In previous studies we identified the transcription/translation factor Y-box-binding protein (YB-1) as a gene that is upregulated in primary melanoma and melanoma metastases when compared to benign melanocytic nevi. To analyze whether YB-1 expression correlates with melanoma progression in vitro and in vivo, we performed expression analysis on melanoma cell lines representing different stages of melanoma progression and on tissues of melanocytic nevi, primary melanoma and melanoma metastases. Our data indicate that compared to benign melanocytes YB-1 expression is increased in melanoma cells in vitro and in vivo and that YB-1 is translocated into the nucleus in invasive and metastatic melanoma cells. To reveal the functional role of YB-1 in melanoma progression we achieved a stable downregulation of YB-1 using shRNA in metastatic melanoma cells. Interestingly, YB-1 downregulation resulted in a pronounced reduced rate of proliferation and an increased rate of apoptotic cell death. In addition, migration and invasion of melanoma cells in monolayer and in a three-dimensional skin reconstruct in vitro was significantly reduced. These effects were accompanied by downregulation of genes involved in proliferation, survival and migration/invasion of melanoma cells such as MMP-2, bcl-2, Cyclin D1, p53 and p16INK4A. Furthermore, melanoma cells with a reduced YB-1 expression showed a decreased resistance to the chemotherapeutic agents cisplatin and etoposide. These data suggest that YB-1 is involved in malignant transformation of melanocytes and contributes to the stimulation of proliferation, tumor invasion, survival and chemoresistance. Thus, YB-1 may be a promising molecular target in melanoma therapy. © 2007 Wiley-Liss, Inc. [source] Fatal malignant melanoma in a child with neurofibromatosis type 1INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 9 2007Yousef Bin Amer MBBS Neurofibromatosis type 1 is an autosomal dominant disease and is considered one of the most commonly inherited diseases in humans. Malignant melanoma has been reported in up to 5% of patients with neurofibromatosis type 1. We report a young Saudi boy with neurofibromatosis type 1 who developed fatal metastatic malignant melanoma arising from giant melanocytic nevi within speckled lentiginous nevus (SLN). [source] Distinction of conjunctival melanocytic nevi from melanomas by fluorescence in situ hybridizationJOURNAL OF CUTANEOUS PATHOLOGY, Issue 2 2010Klaus J. Busam A conjunctival melanocytic nevus may on occasion be difficult to distinguish from melanoma both clinically and histopathologically. An unambiguous correct diagnosis is critical because of major differences in management and prognosis. We evaluated a fluorescence in situ hybridization (FISH) assay, which has previously been shown to be of value for the diagnosis of melanocytic nevi and melanomas of the skin, using probes targeting 6p25 (RREB1), 6q23 (MYB), 11q13 (CCND1) and centromere 6 (CEP6), for its potential to assist in the distinction of conjunctival melanocytic nevi from melanomas. Four melanocytic nevi and eight melanomas of the conjunctiva were analyzed. Two of the melanomas were diagnostically problematic because of suboptimal histopathology. None of the conjunctival melanocytic nevi showed a level of chromosomal aberrations that met FISH criteria for a diagnosis of melanoma. All eight conjunctival melanomas (six unequivocal and two suspicious lesions) met FISH criteria for melanoma. Thus, results from FISH assay targeting 6p25, 6q23, 11q13 and centromere 6 correlated well with the histopathologic diagnoses and supported the histopathologic suspicion in two problem cases. The findings encourage further exploration of this technique as an ancillary method for the work-up of conjunctival melanocytic proliferations. Busam KJ, Fang Y, Jhanwar SC, Pulitzer MP, Marr B, Abramson DH. Distinction of conjunctival melanocytic nevi from melanomas by fluorescence in situ hybridization. [source] Nevi with site-related atypia: a review of melanocytic nevi with atypical histologic features based on anatomic siteJOURNAL OF CUTANEOUS PATHOLOGY, Issue 10 2008Gregory A. Hosler A subset of melanocytic nevi share features with melanoma and nevi with architectural disorder but are biologically inert and to date do not appear to portend an increased risk for the development of malignancy. These benign nevi with certain atypical histologic features cluster among specific anatomic sites and are thus designated nevi with site-related atypia. We categorize these lesions into four main groups: acral, genital, special site and conjunctival, based on anatomy and relative prevalence of specific atypical histologic features. As the literature and our recognition of these lesions continue to grow, our understanding of their biology has not kept pace. [source] G1 cell cycle regulators in congenital melanocytic nevi.JOURNAL OF CUTANEOUS PATHOLOGY, Issue 9 2008Comparison with acquired nevi, melanomas Background:, Congenital nevi are one of the known risk factors for the development of melanoma. However, the magnitude of the risk for both large and small congenital nevi is controversial. Methods:, In order to elucidate the behavior of congenital nevocytes and to define any possible similarities or differences with common nevi and melanomas, we investigated the expression of Ki-67, Rb, p16, cyclin D1, p53 and p21/Waf-1 in 41 congenital nevi, 16 melanomas and 20 acquired common nevi by immunohistochemistry. Results:, Congenital nevi highly expressed p16 (81.82 ± 9.98) but showed limited, if any, reactivity for Ki-67 (1.34% ± 0.89), Rb (0.76% ± 0.94), cyclin D1 (0.21% ± 0.29), p53 (0.54% ± 0.93) and p21 (0.0609% ± 0.32). No statistically significant difference was found between giant and nongiant congenital nevi and between congenital and common nevi for any of the markers. The expression of p16 was significantly higher in congenital nevi than in melanomas (p < 0.0001). On the contrary, the expression of Ki-67, p53, p21, Rb and cyclin D1 was significantly higher in melanomas (p < 0.0001). Conclusion:, Our data regarding the immunohistochemical expression of Rb, p16, p53, cyclin D1 and Ki-67 in congenital nevi indicate that either the alteration of their expression is not an initiating event in melanoma formation or, alternatively, congenital melanocytic nevi may not be the first step in malignant transformation. [source] Cutaneous melanocytoneuroma: the first case of a distinctive intraneural tumor with dual nerve sheath and melanocytic differentiationJOURNAL OF CUTANEOUS PATHOLOGY, Issue 2007Ilan Weinreb Many melanocytic nevi contain areas similar to nerve sheath tumors (NST) and NSTs with melanin have been described. There are some NSTs with at least partial intraneural location, including neurofibromas, plexiform neurofibromas, granular cell tumors and the recently described, dendritic cell neurofibroma with pseudorosettes. We describe the case of an NST with melanocytic differentiation and intraneural location, for which we suggest the term ,melanocytoneuroma' (MCN). It arose in the skin of a 67-year-old woman with no previous history of melanoma or neurofibromatosis. The lesion presented as a papule and histologically consisted of a dermal nodule without junctional melanocytic activity. The lesion comprised an intraneural proliferation of large epithelioid eosinophilic cells with prominent cell borders imparting a ,plant-like' appearance. The cells were also seen within adjacent nerve twigs and were positive for S100, Melan-A, HMB-45, microphthalmia transcription factor and PGP 9.5. The lesion was entirely surrounded by an epithelial membrane antigen-positive-perineurial coat and the individual tumor cells were invested by laminin and collagen type-IV-positive basal lamina-like material. The lesion did not show any evidence of atypia and following complete excision, no recurrence has been documented. In conclusion, this unusual lesion represents an intraneural proliferation with melanocytic and nerve sheath cell differentiation, to which we have accorded the appellation, MCN. [source] Low prevalence of RAS-RAF -activating mutations in Spitz melanocytic nevi compared with other melanocytic lesionsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 6 2007James O. Indsto One of 22 (4.5%) SN tested showed an HRAS G61L mutation. Another lesion, a ,halo' SN, showed a BRAF V600E (T1796A) mutation. BRAF V600E mutations were found in two thirds (20/31) of CBN, while a further 19% (6/31) showed NRAS codon 61 mutations. One third of CMM (10/30) had various BRAF mutations of codon 600, and a further 6% (2/31) showed NRAS codon 61 mutations. Seventeen SN tested for loss of heterozygosity (LOH) at 9p and 10q regions, known to be frequently deleted in melanoma, showed LOH at the 9p loci D9S942 and IFNA. A further lesion was found with low-level microsatellite instability at one locus, D10S214. The low rate of RAS-RAF mutations (2/22, 9.1%) observed in SN suggests that these lesions harbor as yet undetected activating mutations in other components of the RAS-RAF-MEK-ERK-MAPK pathway. Germline DNA from members of 111 multiple-case melanoma families, representing a range of known (CDKN2A) and unknown predisposing gene defects, was analyzed for germline BRAF mutations, but none was found. [source] Atypical nevi of the scalp in adolescentsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 5 2007Giujeppe Fabrizi Background:, A few reports in the literature point out that in special areas of the body, nevi can have peculiar pseudomelanomatous features. In our routine work, we have met few examples of atypical nevi with peculiar features on the scalp of teenagers. To evaluate the frequency and the biological behaviour of these lesions, we have conducted a complete survey on melanocytic lesions on the scalp in a significant group of patients. Materials and methods:, Thirty-nine nevi of the scalp were from adolescents (12,18 years), 160 from adults, and 30 from children below the age of 12 years. Results:, About 10% of the melanocytic nevi of the scalp of adolescents have atypical cytological and architectural aspects that are different from those seen in Clark's dysplastic nevus. The most striking features were the presence of large bizarrely shaped nests scattered disorderly along the junction with follicular involvement. Other findings were pagetoid spread of cells above the junction and the discohesive pattern of the melanocytes in the nests. Mild cytological atypia was present but less significant. Such distinctive aspects are not found in nevi of the same site in adults or younger children. The general pattern of these atypical nevi of the scalp of adolescents closely recalls that of the so-called atypical nevi on special sites, i.e. nevi on mammary line, genitalia and body's folds. Despite the architectural and cytological atypia, clinical follow-up does not show any tendency to recur or proclivity to malignant behaviour. Conclusions:, Despite their similarities with melanoma, the nevi with atypical features of the scalp of adolescents are probably an entirely benign entity, at least at the moment of their excision. However, although benign, the relationship of this peculiar group of nevi with melanomas developed in adulthood remains entirely unknown, and the complete excision with conservative margins seems a recommendable procedure. [source] Nestin expression in cutaneous melanomas and melanocytic neviJOURNAL OF CUTANEOUS PATHOLOGY, Issue 5 2007Svetlana Brychtova Background:, Nestin is one of the intermediate filaments that are expressed in proliferating neural progenitor cells during development of the central nervous system (CNS) and peripheral nervous system. Postnatal re-expression of the protein occurs mainly under pathological conditions, including injury and neoplasia. In this study, nestin expression was detected in both benign and malignant melanocytic skin lesions and its diagnostic relevance was then evaluated. Methods:, Altogether 139 bioptic tissue samples consisting of 42 nodular melanomas, 32 superficial spreading melanomas, 12 metastatic melanomas, 10 dysplastic nevi and 43 common melanocytic intradermal and dermoepidermal nevi were analysed using indirect immunohistochemical staining. Results:, We demonstrated that nestin immunostaining was significantly increased in melanomas where it correlated with more advanced stages of the disease. Conclusion:, We conclude that expression of the intermediate filament protein nestin might be an indicator of tumor dedifferentiation and more aggressive behaviour. Furthermore, we suggest that nestin might be a relevant marker of tumorous and non-tumorous angiogenesis. [source] Protein expression of melanocyte growth factors (bFGF, SCF) and their receptors (FGFR-1, c-kit) in nevi and melanomaJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2007K. A. Giehl Background:, Basic fibroblast growth factor (bFGF) and stem cell factor (SCF) are essential growth factors for melanocytes which carry the receptors FGFR-1 for bFGF and c-kit for SCF. Because both factors may be involved in melanoma development, the expression of bFGF/FGFR-1 and SCF/c-kit was investigated in melanocytic tumors of different progression stages. Methods:, Fifty primary melanomas and 44 melanocytic nevi were analyzed for the expression of SCF, c-kit, bFGF, and FGFR-1 by immunohistochemistry. Results:, In melanoma, SCF and c-kit were expressed in 76 and 84%, respectively, and coexpressed in 66%. bFGF and FGFR-1 were expressed in 45 and 86%, respectively, and coexpressed in 46%. In melanocytic nevi, SCF was expressed in 23% and c-kit in 70% while coexpression was more common in dysplastic (39%) than non-dysplastic subtypes (8%). bFGF and FGFR-1 were expressed in 55 and 67%, respectively, while coexpression was found in 47% but varied considerably between different histological subtypes. Conclusions:, SCF and c-kit were frequently expressed by melanomas and dysplastic nevi suggesting an autocrine growth mechanism as described for bFGF. In both nevi and melanoma, c-kit was almost exclusively found in the epidermis while bFGF was more common in the dermis. Thus the growth factor/receptor expression seems to depend on the cutaneous localization of the melanocytic tumors. [source] Melanocytic nevi are associated with neurofibromas in neurofibromatosis, type I, but not sporadic neurofibromas.JOURNAL OF CUTANEOUS PATHOLOGY, Issue 8 2005A study of 226 cases Background:, Neurofibromatosis, type 1, is associated with cutaneous melanin pigmentation, but an association with ordinary melanocytic nevi has not been described. Methods:, This retrospective case-control study was designed to see if neurofibromas in patients with neurofibromatosis, type 1 (NF-1) differ from sporadic neurofibromas (SN) in their incidence of associated melanocytic nevi and other histologic features. Slides from 114 NF-1 were compared with 112 SN and 300 intradermal melanocytic nevi (IDN). Results:, Small lentiginous melanocytic nevi were identified over 13 NF-1 (11%) but no SN (P = 0.0002). Compared with other NF-1, NF-1 with nevi were more frequently associated with melanocytic hyperplasia, giant melanosomes and diffuse neurofibroma (P < 0.03). Compared with SN, NF-1 were also more frequently associated with melanocytic hyperplasia, lentigo simplex-like changes, diffuse neurofibroma and plexiform neurofibroma (P < 0.001). Sebaceous hyperplasia (14%), dermal elastosis (9%), lipomatous change (8%), epithelial cysts (4%) and keratin granulomas or folliculitis (3%) were not significantly different in prevalence between NF-1, SN and the control group of IDN. Conclusions:, This study suggests that there is a difference in the potential for melanocytic proliferation in NF-1 compared with SN. NF-1, SN and IDN are associated with a similar range of incidental histologic changes. [source] Loss of claudin-1 expression in tumor-associated vessels correlates with acquisition of metastatic phenotype in melanocytic neoplasmsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 8 2005Michael L. Cohn Recent studies have suggested that some metastatic solid tumors lack claudin expression. It is unknown whether claudins play a role in cutaneous melanoma. Immunohistochemical studies were performed on tissue microarrays containing 19 benign melanocytic nevi (BN), 21 dysplastic nevi (DN), 23 primary malignant melanomas (MMs), and 31 metastatic melanomas (MMMs) using a polyclonal anti-claudin-1 antibody. Immunoreactivity in tumor cells and associated vessels was graded by intensity and by percentage of reactive cells. Normal epidermis served as internal control (3+ labeling). Cases with at least 2+ labeling in more than 25% of the cells were considered positive. Claudin-1 expression was present in 37% of BN, 24% of DN, 26% of MM, and 3.2% of MMM. Tumor-associated vessels showed the following results: 11 of 19 (58%) in BN, 14 of 21 (67%) in DN, 17 of 23 (74%) in MM, and 6 of 31 (19%) in MMM. A significant loss of expression was noted between MMM and all other lesions in tumor cells and associated vessels. There was no significant difference between BN, DN, and MM. Within primary melanomas, there was a significant correlation between expression of claudin in tumor cells and Clark level/Breslow thickness. Also significant was a decreased expression of claudin in tumor vessels of lesions with higher Breslow thickness or Clark level. These data suggest that loss of claudin-1 may play a significant role in the acquisition of metastatic phenotype in cutaneous melanoma. [source] Pleiotrophin expression correlates with melanocytic tumor progression and metastatic potentialJOURNAL OF CUTANEOUS PATHOLOGY, Issue 2 2005H. Wu Background:, Gene expression profiling of melanoma and nevic tissue has demonstrated that pleiotrophin (PTN) is significantly overexpressed in human melanomas. Methods:, To further evaluate PTN expression in melanocytic lesions, protein immunohistochemistry was performed on the spectrum of melanocytic lesions. Results:, Melanocytic nevi were consistently negative (n = 58). In contrast, the great majority of metastatic melanomas were positive (33/34, 97%). The analysis of 34 primary melanomas demonstrated PTN positivity in 20 lesions while 14 lesions were negative. Within the primary melanomas, PTN immunoreactivity was associated with metastasis (p = 0.0004) and decreased melanoma-related survival (p = 0.0444). Univariate analysis of PTN immunoreactivity predicted an increased risk for metastasis (relative risk 9.1, p = 0.003). Conclusions:, The results of this study confirm previous gene profiling data showing differential PTN expression between melanocytic nevi and melanomas. In addition, lesional PTN expression is associated with metastatic potential and may be a prognostic factor for melanomas. [source] BRAF V599E Mutation is Not Age Dependent: It is Present in Common Melanocytic Nevi in Both Children and AdultsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2005J. Cohen BRAF encodes a serine-threonine kinase, which acts in the RAS/RAF/MAPK pathway transducing regulatory signals from RAS to MEK1/2. Somatic mutations in BRAF have been identified in 53,80% of primary melanomas and 70,90% of common melanocytic nevi. More than 90% of these mutations consist of a valine to glutamate substitution at codon 599 (V599E) of exon 15. While a high prevalence of BRAF mutations in common melanocytic nevi has been reported in adults, nevi in children have not been studied. Of interest, we have previously shown that Spitz nevi in children do not harbor mutations in BRAF. To investigate the association of BRAF mutations with patient age, we studied common melanocytic nevi in children for the V599E activating mutation. Tumor cells were microdissected from 6 common melanocytic nevi in children 10 years of age or younger, and analyzed for the V599E mutation in BRAF by allele-specific PCR and gel electrophoresis. In 6 of 6 (100%) nevi, the V599E mutant allele was observed. Our data suggest that similar genetic pathways are involved in the development of common melanocytic nevi in children and adults. The absence of BRAF mutations in Spitz nevi in children is therefore associated with tumor type, not patient age. [source] Skp2 and p27kip1 expression in melanocytic nevi and melanoma: an inverse relationship,JOURNAL OF CUTANEOUS PATHOLOGY, Issue 10 2004Qing Li Background:, S-phase kinase associated protein-2 (Skp2) ubiquitin ligase p45SKP2 is important in the degradation of p27kip1 (a cyclin dependent kinase inhibitor) and progression through the G1-S cell-cycle checkpoint. Low levels of p27 and high levels of Skp2 are related to poor prognosis in some cancers. Methods:, Clinicopathologic features and immunohistochemical expression of Skp2 and p27kip1 were investigated in 198 melanocytic proliferations: 21 melanocytic nevi, 23 melanoma in situ, 119 primary melanoma, and 35 metastatic melanoma samples. Comparative and survival analyses were performed. Results:, Progressive and significant increases and decreases in the nuclear expression of Skp2 and p27kip1, respectively, was identified moving from melanocytic nevi (0.05 ± 0.2/85 ± 15) to melanoma in situ (3 ± 2/45 ± 20) to primary cutaneous melanoma (12 ± 9/30 ± 25) to metastatic melanoma (25 ± 15/15 ± 20) (p , 0.006). Expression of these proteins also significantly correlated with increasing American Joint Committee on Cancer (AJCC) T (tumor) classification and AJCC stage (p , 0.01). Moreover, the level of these two proteins exhibited a significant inverse relationship (r = ,0.4, p = 0.0001). Skp2 cytoplasmic labeling index of >20% predicted worse 10-year overall survival (38% vs. 86%, p = 0.04) in primary melanoma. Neither p27 nor Skp2 nuclear expression impacted significantly on prognosis. Conclusions:, Gain of Skp2 and loss of p27kip1 protein expression are implicated in melanoma progression where the level of p27kip1 may be regulated by targeted proteolysis via Skp2. Cytoplasmic expression of Skp2 defines a subset of aggressive melanomas and could represent another pathway of deregulation of the cell cycle. [source] Melanocytic nevi of the breast: a histologic case-control studyJOURNAL OF CUTANEOUS PATHOLOGY, Issue 2 2004F. Rongioletti Background:, Melanocytic nevi in the genital, acral, and flexural sites often display clinical and histologic features that may simulate melanoma. We verified whether this is the case also for nevi of the breast. Methods:, Eleven dermatopathologists, from nine Italian Institutions, collected the specimens of melanocytic lesions from the breast and other body sites, excluding the acral, genital, and flexural areas, as controls. Cases and controls were matched for sex and age. All nevi were observed ,blindly' and simultaneously by all participants. For each lesion, 10 histological parameters were analyzed: asymmetry, absence of lateral demarcation of melanocytes, lentiginous proliferation, nested and dyshesive pattern, intraepidermal melanocytes above the basal layer, involvement of the hair follicle, absence of maturation of dermal melanocytes, melanocytic atypia, fibroplasia of the papillary dermis, and lymphocytic dermal infiltrate. Each parameter was scored 2 when present and 1 when absent or not valuable. A total score was calculated for each lesion. Results were statistically analyzed by the chi-square test and the Mann,Whitney U -test. Results:, One hundred and one nevi came from the breast area and 97 from elsewhere. Breast nevi exhibited significantly more atypical features than nevi from other sites. In particular, breast nevi with intraepidermal melanocytes, melanocytic atypia, and dermal fibroplasia were significantly more numerous. We did not find any sexual difference. Conclusions:, To avoid undue concerns, dermatopathologists should be aware that melanocytic nevi of the breast may show a high degree of atypical features. [source] Cadherin expression pattern in melanocytic tumors more likely depends on the melanocyte environment than on tumor cell progressionJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2004Sven Krengel Background:, Adhesion molecules have been assigned an important role in melanocytic tumor progression. By the loss of E-cadherin, melanocytes might escape the control of neighbouring keratinocytes. Although in vitro data support this hypothesis, there are yet no conclusive immunohistochemical results on cadherin expression in melanocytic tumors. Objective:, To gain detailed insight in the expression of cadherins and their cytoplasmic binding partners, the catenins, in various types of benign and malignant melanocytic neoplasms. Methods:, Immunohistochemical analysis of the expression of E-, P-, and N-cadherin and ,-, ,-, and ,-catenin in compound and dermal nevi, Spitz nevi, blue nevi, ultraviolet B (UVB)-irradiated nevi, and malignant melanomas of various tumor thickness. Results:, In both nevi and melanomas, E-cadherin expression in melanocytic cells decreased, following a gradient from junctional to deeper dermal localization. The pattern of E-cadherin expression was more heterogeneous in melanomas than in nevi. In some melanomas, E-cadherin was only weakly positive in the epidermal tumor cells. P-cadherin expression was similar to that of E-cadherin. N-cadherin expression in melanocytic lesions was a rare finding, however, a small percentage of melanomas showed expression in some cell nests. Some Spitz nevi exhibited strong N-cadherin immunoreactivity. Most melanocytic cells were ,- and ,-catenin-positive and ,-catenin-negative. UVB irradiation did not influence the expression of cadherins and catenins in melanocytic nevi in vivo. Conclusions:, It is presumed that the gradual loss of E-cadherin expression represents a reaction of melanocytic cells to altered conditions in the dermal environment, e.g. lack of contact to keratinocytes, or new contact with dermal extracellular matrix molecules, respectively. Melanoma cells apparently are less dependent on these environmental factors and, therefore, show a more heterogeneous expression pattern. This might be of importance for the adaptation of the tumor cells to local requirements. However, in view of our results, a causative role of (loss of ) E-cadherin or (gain of ) N-cadherin for melanocytic tumor progression still remains to be proven. [source] Histologic features of melanocytic nevi seen in association with mycosis fungoidesJOURNAL OF CUTANEOUS PATHOLOGY, Issue 10 2003Jennifer M. McNiff Background:, Many different tumors have been reported to occur simultaneously as collision lesions. To date, no such events have been reported between mycosis fungoides (MFs) and melanocytic neoplasms. Methods:, Two cases are presented in which patches of MF were superimposed on melanocytic nevi. In addition, 967 biopsies of MF from 411 patients were identified in an 8-year retrospective database search. Patient pathology history summaries were reviewed to identify inflamed nevi, atypical nevi, and melanoma submitted for histologic evaluation from this population. Results:, The occurrence of MF in a congenital nevus was associated with a halo phenomenon restricted to the affected region of the nevus in one patient. In the other patient, nests of two morphologies (lymphocytic and melanocytic) in the same biopsy presented a potentially confusing histologic picture. No other cases of MF superimposed on a nevus were identified in 967 biopsies from 411 patients with a histological diagnosis of MF seen over the past 8 years. In this population, 57 biopsies of melanocytic lesions were identified from 28 patients, including three atypical nevi and three melanomas. Conclusions:, The presence of MF superimposed on a nevus is rare and may lead to confounding histologic features or the development of a halo nevus phenomenon. [source] | |||||||||||||||||||||||||